Effect of the rs997509 polymorphism on the association between ectonucleotide pyrophosphatase phosphodiesterase 1 and metabolic syndrome and impaired glucose tolerance in childhood obesity.
BACKGROUND
Variants on the nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP-1) gene have been associated with obesity and insulin resistance. Because insulin resistance is a pivotal factor in the development of metabolic syndrome (MS) and impaired glucose tolerance (IGT), we aimed to test the association between the K121Q and rs997509 ENPP-1 variants with obesity, MS and IGT in obese children and adolescents.


METHODS
We screened 809 children, 409 obese and 400 lean controls. Obese subjects underwent a standard oral glucose tolerance test, whole body insulin sensitivity index (WBISI) and homeostasis model assessment (HOMA) were calculated.


RESULTS
No difference in prevalence for K121Q and rs997509 polymorphisms between obese and controls (P > 0.05) were observed. Obese children carrying the rs997509 rare allele showed higher insulin (P = 0.001), HOMA (P < .001) and lower WBISI values (P = 0.04) compared with common allele homozygous. A similar observation was done for K121Q variant, with 121Q allele carriers showing higher insulin (P = 0.03) and HOMA (P = 0.04) values than 121K homozygotes. Moreover, subjects carrying the rs997509 rare allele had higher risk of MS (odds ratio 2.4, 95% confidence interval: 1.3-4.3) and IGT (odds ratio 4.7, 95% confidence interval: 1.9-11.4) than common allele homozygotes. Evaluating combined effects of both polymorphisms, which are in strong linkage disequilibrium, we showed that the effect on insulin sensitivity was due to the rs997509 T variant.


CONCLUSIONS
We conclude that the ENPP1 rs997509T allele can predispose obese children to MS and IGT and that this variant might drive the association between the ENPP1 121Q allele and insulin resistance.
Santoro
Nicola
N
Dipartimento di Pediatria, Seconda Università di Napoli, Via Luigi De Crecchio No. 2, 80138 Napoli, Italy.
Cirillo
Grazia
G
Lepore
Maria Grazia
MG
Palma
Alfonsina
A
Amato
Alessandra
A
Savarese
Piera
P
Marzuillo
Pierluigi
P
Grandone
Anna
A
Perrone
Laura
L
Del Giudice
Emanuele Miraglia
EM
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D018149:Glucose Intolerance / Q000235:genetics*; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics*; D009765:Obesity / Q000235:genetics*; D010727:Phosphoric Diester Hydrolases / Q000235:genetics*; D011110:Polymorphism, Genetic; D011755:Pyrophosphatases / Q000235:genetics*
D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases